The goal of this project is to study in vitro transformation induced by chemicals in cells that are engineered to inappropriately express cellular oncogenes or other genes likely to be involved in neoplastic processes. There are several advantages to the use of oncogene primed cells in the investigation of mammalian biology. One advantage is the ability to use these gene constructs to investigate control of gene activity in vitro. Regulatory regions can be spliced to a marker gene to determine when and where a gene under the control of these sequences is expressed. This approach requires the construction of a proto-oncogene that specifically addresses the question at hand. A second advantage to the use of proto- oncogenes is the ability to disrupt endogenous genes with a cloned DNA sequence. The sites of insertion of a proto-oncogene are believed to be random. Therefore, it is expected that any gene would be disrupted with a finite probability. The integrated DNA serves as a tag to identify the affected gene and allows molecular cloning of the gene based on homology to the inserted sequence.